microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual specificity phosphatase 6 expression.
- Author:
Heejin LEE
1
;
Chongtae KIM
;
Hoin KANG
;
Hyosun TAK
;
Sojin AHN
;
Sungjoo Kim YOON
;
Hyo Jeong KUH
;
Wook KIM
;
Eun Kyung LEE
Author Information
- Publication Type:Original Article
- MeSH: Carcinoma, Hepatocellular; Cell Line; Cell Survival; Clone Cells; Doxorubicin; Drug Resistance; Dual Specificity Phosphatase 6*; Dual-Specificity Phosphatases*; Ectopic Gene Expression; Fluorouracil*; Humans; Lentivirus; MicroRNAs
- From:Experimental & Molecular Medicine 2017;49(5):e327-
- CountryRepublic of Korea
- Language:English
- Abstract: Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression.
